Developing strategies to control and prevent congenital infection with cytomegalovirus (CMV) represents a major priority in perinatal medicine. CMV infection is the most common congenital infection in the developed world. The condition occurs in 0.5 to 2% of all births and is responsible for a wide range of neurodevelopmental disabilities in newborns. Of these disabilities, the most common is sensorineural hearing loss (SNHL), which occurs in up to 15% of all congenitally infected children. The outcome of SNHL is improved when antiviral therapy (ganciclovir) is administered to infants with neurological involvement who are congenitally infected with CMV. However, other forms of neurological injury associated with symptomatic congenital CMV may be irreversible.
Because pre-conceptual maternal immunity to CMV reduces the severity of injury caused by congenital CMV, the development of vaccines is considered to be of high priority. See, e.g., US Patent Publication No. 2010/0285059. A number of CMV vaccines are currently being evaluated in clinical trials, including live attenuated vaccines and subunit recombinant vaccines. Better elucidation of the determinants of the maternal immune response that result in protection of the fetus will help in prioritizing future vaccine studies for prevention of congenital infection.
Ideally, immunizations for CMV would first be evaluated in animal models prior to human clinical trials. Unfortunately, the strict species specificity of CMVs precludes any meaningful evaluation of candidate human CMV vaccines for protection in animal models. Although laboratory animals will engender immune responses to the candidate vaccines being evaluated in clinical trials, which allow study of safety and immunogenicity, laboratory animals cannot be infected with human CMV. As a result, the ability to analyze the protective effect of vaccines against experimental disease is restricted, and investigators have turned to species-specific animal CMVs to generate models of pathogenesis and immunity.
Among the small animal models of congenital CMV infection, the guinea pig cytomegalovirus (GPCMV) offers some unique advantages compared with rodent models. Chief among these advantages is the fact that GPCMV crosses the guinea pig placenta, causing infection in utero. For this reason, the guinea pig is well suited to the study of vaccines designed to interrupt vertical virus transmission. (Schleiss, ILAR Journal 47:65-72 (2006)). A limitation of the model, however, is that only one strain of the virus is available, the ATCC/22122 strain, discovered by Hartley in 1957 (Hartley J W, Rowe W P, Huebner R J. 1957. Serial propagation of the guinea pig salivary gland virus in tissue culture. Proc Soc Exp Biol Med 96:281-285). Thus, there is a current need for an alternative isolate of GPCMV.